Effects of Anesthesia on Pediatric Brain MR Imaging Julie Harreld, MD St. Jude Children’s Research Hospital Memphis, TN

Anesthesia and MRI • Pediatric MRI highly dependent on anesthesia – All young children (1.98, rCBF>1.25 = high-grade glioma (Hayyemez et al, 2005)

– Lesion:normal brain • rCBV > 2.1 =recurrence (vs. radiation necrosis) (Mitsuya et al, 2010) • rCBV>1.75 predicts progression (Law et al, 2006 & 2008)

rCBV > 2.1 (tumor)

Ratios • Tumor: normal brain ratio may change with anesthesia – Vasoreactivity of tumor neovascularity likely differs from normal vessels

• GM:WM ratio – Generally accepted that CBF and GM/WM ratios decrease with age (Huisman 2004; Biagi 2007; Ogawa 1989) – Trends altered with anesthesia

Adapted from Cenic et al, 2005 Awwad, Harreld et al, ISMRM 2013

Vessel conspicuity on SWI • Veins appear dark on SWI due to deoxyhemoglobin • Increasing CBF, ETCO2 decreases venous deoxy-Hb (more oxygenated venous blood), decreasing venous conspicuity [BOLD effect] (Sedlacik et al, 2010) – Could lead to underestimation of extent of vascular lesions (ex: AVM) – Could impact attempts to stage tumors with SWI (Hori et al, 2010)

Sevoflurane. CBF=78.9, CBV=10.5, ETCO2 =51

Propofol. CBF=40.9, CBV=5.65, ETCO2 =37.25

CSF Artifact on FLAIR • Artifactual CSF signal intensity in sulci and cisterns can mimic or obscure leptomeningeal disease • Attributed variably to – Anesthetic agents – Supplemental O2 administered with anesthesia • Attributed to T1 effects

– Recent study found effect of anesthetic agent to be dominant (Harreld et al, ASNR 2012)

Variable sulcal signal intensity in patients without leptomeningeal disease.

CSF Hyperintensity on FLAIR– Artifact or Disease?

Scan 1. Increased signal in sulci. 6yo M with L frontoparietal skull Ewing sarcoma. Post-contrast FLAIR image (left) [3T; TR10000, TE 108, TI 2604.7, 20 ch head coil] shows diffusely increased signal in sulci.

CSF Hyperintensity on FLAIR– Artifact or Disease?

Scan 2. Increased signal in sulci has decreased. Same patient 3.5 months later, no intervening treatment. Same magnet and imaging parameters. Post-contrast FLAIR image (left) shows decrease in increased signal in sulci. Only difference: Sevoflurane GA on Scan 1 (see oral airway device) and propofol on Scan 2 (see NC).

fMRI CBF Stimulus

Neuron

Cerebral Metabolism

Relatively less extraction O2, so MORE O2-Hb (paramagnetic), in that volume of blood

Signal in activated volume ( % paramagnetic DeoxyHb, which signal )

BOLD EFFECT

• Neurovascular coupling – Neurons – Astrocytes • Coupling of post-synaptic activity to metabolism and vascular response (CBF)

– Vessels

Anesthetic Actions on Neurovascular Coupling 5

3 1

2

Stimulus

Neuronal activity

CBF 8 7

4

Signal

Metabolism 6 1 Optimal Stimulus Frequency Isoflurane

2 Latency Propofol Isoflurane (doserelated) ∆ ketamine, fentanyl

3 Neuronal Activity GABA-ergic: Propofol Pentobarbital Isoflurane

4 Glutamatergic transmission Ketamine, pentobarbital

Buxton 2010; Franceschini 2010; Magistretti 2006, 2009; Masamoto 2012; Qiu 2008; Szabo 2009; Veselis 2005

5 CBF propofol,fentanyl, diazepam,midazolam isoflurane,sevoflurane

7 CBF-Metabolic Coupling volatile anesthetics (thanes)

6 Cerebral Metabolism 8 Spatial Coordination propofol,fentanyl, diazepam,midazolam isoflurane,sevoflurane halothane

isoflurane

fMRI • Propofol (and other IV anesthetics) decrease cortical activity and CBF – CBF response (coupling) • preserved at sedative, but not hypnotic, concentrations (Veselis 2005)

– Latency • increases with propofol (Franceshini 2010)

• Volatile anesthetics (e.g. sevoflurane, isoflurane) – Disrupt CBF-Metabolic coupling – May affect optimal stimulus frequency – May alter spatial coordination of activation and BOLD signal

Conclusion • Significant challenge in pediatric neuroimaging • Be cautious when interpreting quantitative MR imaging in anesthetized children • Be aware of effects on anatomic images (FLAIR, SWI) • Possible solutions – – – –

Standardized anesthesia New “normals” for CBF, CBV under anesthesia Consideration in statistical analysis More research characterizing effects in children • More sensitive than adults to vasodilatory effects sevoflurane • Data in adults may not apply to children

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